Glioblastomas (GBM) exhibit a remarkable tumor cell heterogeneity, which contributes to the overall regenerative and aggressive disease traits. Recent studies in our laboratory's and others' strongly support the existence of a cellular hierarchy within GBM in which brain tumor initiating cells (BTICs) at the apex are the driving force of disease recurrence and resistance to current therapies. It is imperative to consider the intimate and dynamic interactions between BTICs and their immediate environments in perivascular, hypoxic, and necrotic regions within the tumor. These locations serve as functional niches for BTICs and facilitate access to various factors and interacting partners that promote their growth- and ultimately of the overall tumor. While clinical studies have uncovered high platelet counts as a negative prognostic marker for survival outcomes in GBM patients, there is no study to functionally elucidate a role for platelets in this highly aggressive disease. The proposed studies aim to uncover a biological role for platelets in driving the growth and stemness qualities specifically of BTICs, which have been histologically detected in BTIC-related niches in primary clinical specimens. As location serves a strong purpose within the context of BTICs, successful characterization of potential crosstalk between platelets and BTICs will offer a new clinical perspective into GBM and inform of a novel treatment paradigm to target these specific cell-to-cell interactions. The development of effective therapeutics to disrupt platelets-BTIC interactions may improve the long-term clinical outcomes of GBM patients undergoing current standard therapies.